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No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We evaluated the effects of an early long\u2010term treatment (<jats:styled-content style=\"fixed-case\">ELTT<\/jats:styled-content>; 17 weeks), started before seizure onset (<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>45), with fluoxetine (selective 5\u2010HT\u2010reuptake inhibitor), duloxetine (dual\u2010acting 5\u2010HT\u2010noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive\u2010like behaviour in the WAG\/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6\u2010month\u2010old) rats after a chronic 7 weeks treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">ELTT<\/jats:styled-content> with all antipsychotics did not affect the development of seizures, whereas, both <jats:styled-content style=\"fixed-case\">ELTT<\/jats:styled-content> haloperidol (1\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup>) and risperidone (0.5\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup>) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup>) and duloxetine (10\u201330\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup>) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> reduced immobility time while at 10\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> day<jats:sup>\u22121<\/jats:sup> an increase was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive\u2010like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive\u2010like behaviour.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13121","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T11:05:56Z","timestamp":1425553556000},"page":"3177-3188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Antidepressants but not antipsychotics have 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